News & Perspective

FDA-approved brexanolone alleviates postpartum depression symptoms with rapid onset and durable effects

Psychiatry
3 months ago, OP Editor

Intravenous administration of brexanolone (Zulresso) to patients with moderate to severe postpartum depression for 60 hours significantly reduces the depressive symptoms and provides durable effects.1 Yet, the FDA-approved drug may induce excessive sedation and other adverse events, which requires restricted distribution with medical supervision.1,2 These findings were published in a recent issue of The Lancet.1

Mothers with postpartum depression have a higher risk of morbidity and mortality, which could lead to detrimental consequences of the disease impacting their children and families.3,4 However, current medications available for postpartum depression women, such as selective serotonin-reuptake inhibitors (SSRIs), are not designed to respond to the hypothesized cause of the disorder, resulting in at least a week-long efficacy onset and low remission rate.1 An efficacious postpartum depression-specific therapy has been long awaited. In March 2019, the U.S. Food and Drug Administration (FDA) approved brexanolone intravenous injection, the first treatment approved specifically for postpartum depression.2

The phase 3 trials of the 60-hour (h) infusion of brexanolone consisted of two randomized, double-blinded and placebo-controlled studies.1 The first study assigned 138 women with severe postpartum depression to brexanolone injection 60μg/kg/h (BRX60), brexanolone injection 90μg/kg/h (BRX90), or placebo, while the second assigned 108 patients with moderate postpartum depression to BRX90 or placebo.1 Measurements assessing the change in depressive symptoms were performed during inpatient stay and two follow-up visits.1

Brexanolone demonstrated rapid onset of antidepressant efficacy, with a significant mean difference in HAM-D total score in BRX60 group versus the placebo group at 60h (5.5, 95% CI: 8.8 to 2.2, p=0.0013).1 The pooled analysis revealed that the reduction in the HAM-D total score from baseline was also significantly higher in BRX90 group than the placebo group at 60h for patients without other antidepressant treatment (LS mean difference=4.3, 95% CI: 6.5 to 2.2, p<0.0001).1

Brexanolone infusion also illustrated durable response of the medication. The proportion of both brexanolone groups achieving remission (HAM-D total score ≤7) at day 30 was higher than the placebo group.1 The decrease in HAM-D total score at day 30 was statistically higher in BRX60 group than the placebo group (p=0.0044).1

In a both BRX60 and BRX90 groups, the most common adverse events were headache, dizziness and somnolence.1 One participant from the BRX90 group experienced drug-related serious adverse events (syncope and altered state of consciousness) with moderate intensity, while two (4%) other participants receiving BRX90 reported fatigue and presyncope.1 4% of BRX recipients experienced excessive sedation, which resolved within 90 minutes after the immediate cessation of infusion; all patients who lost consciousness regained consciousness within 15 minutes after cessation of infusion.1

Since excessive sedation and sudden loss of consciousness were recorded, brexanolone infusion is limited by restricted distribution at qualified healthcare providers, for careful and close supervision of the patients.2 The authors also noted limitations for the studies, as the participants represent the population of moderate to severe postpartum depression patients in the United States, and long-term efficacy remains unclear.1

In conclusion, the administration of brexanolone alleviated the depressive symptoms among patients diagnosed with moderate to severe postpartum depression with a rapid onset of durable effects.1 However, close monitoring and restricted distribution of the medication are required.2

 

1. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-70.

2. FDA approves first treatment for post-partum depression. U.S. Food and Drug Administration. (Accessed May 23, 2019, at https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-post-partum-depression)

3. Alexander JL. Quest for timely detection and treatment of women with depression. J Manag Care Pharm. 2007;13(9 suppl A):S3-11.

4. Gavin NI, Gaynes BN, Lohr KN, et al. Perinatal depression : a systematic review of prevalence and incidence. Obstet Gynecol. 2005:106(5 Pt 1):1071-83.

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